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Small RNA profiling of influenza A virus-infected cells identifies miR-449b as a regulator of histone deacetylase 1 and interferon beta. PLoS One 2013;8(9):e76560

Date

10/03/2013

Pubmed ID

24086750

Pubmed Central ID

PMC3784411

DOI

10.1371/journal.pone.0076560

Scopus ID

2-s2.0-84884664724 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

The mammalian antiviral response relies on the alteration of cellular gene expression, to induce the production of antiviral effectors and regulate their activities. Recent research has indicated that virus infections can induce the accumulation of cellular microRNA (miRNA) species that influence the stability of host mRNAs and their protein products. To determine the potential for miRNA regulation of cellular responses to influenza A virus infection, small RNA profiling was carried out using next generation sequencing. Comparison of miRNA expression profiles in uninfected human A549 cells to cells infected with influenza A virus strains A/Udorn/72 and A/WSN/33, revealed virus-induced changes in miRNA abundance. Gene expression analysis identified mRNA targets for a cohort of highly inducible miRNAs linked to diverse cellular functions. Experiments demonstrate that the histone deacetylase, HDAC1, can be regulated by influenza-inducible miR-449b, resulting in altered mRNA and protein levels. Expression of miR-449b enhances virus and poly(I:C) activation of the IFN╬▓ promoter, a process known to be negatively regulated by HDAC1. These findings demonstrate miRNA induction by influenza A virus infection and elucidate an example of miRNA control of antiviral gene expression in human cells, defining a role for miR-449b in regulation of HDAC1 and antiviral cytokine signaling.

Author List

Buggele WA, Krause KE, Horvath CM

Author

Katherine E. Krause MD Adjunct Instructor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cell Line
Gene Expression Regulation
Histone Deacetylase 1
Humans
Influenza A virus
Interferon-beta
MicroRNAs
Sequence Analysis, RNA